AFIP Wednesday Slide Conference - No. 10
20 November 1996

Conference Moderator: Dr. Michael A. Eckhaus
Diplomate, ACVP
NCRR LSS SSB Bldg. 28A Rm. 117
28 Library Dr. MSC 5210
Bethesda, MD 20892-5210

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Case I - 96-7481 (AFIP 2550490)

Signalment: A three-month-old female SWRX9 recombinant inbred mouse (Mus musculus).

History: This RI line has a published history of a high incidence of ovarian cancer that metastasizes as the mice get older.

Gross Pathology: The mouse was submitted alive and active. The ovaries were both enlarged (0.5 cm in diameter), firm and dark red in color. No other visceral abnormalities were observed.

Laboratory Results: None.

Contributor's Diagnosis and Comments: Mouse juvenile ovarian granulosa cell tumor. Etiology: This is a polygenic phenotype of this RI line. At least three genes have been identified involved in the pathogenesis of this neoplasm.

This is a well-defined genetic model of a rare neoplasm in the mouse that closely resembles the juvenile ovarian cancers that young girls develop. Comparison to cases in the AFIP archives has shown remarkable morphologic and clinical similarities between the ovarian tumors in these two species.

AFIP Diagnosis: Ovary: Granulosa cell tumor, SWRX9 mouse, rodent.

Conference Note: The SWR-derived mouse represents a valuable addition to animal models available to study ovarian tumorigenesis. Common features of granulosa cell tumors (GCT) in SWR mice and juvenile granulosa cell tumor in young human females include early onset in ovaries with intact oocytes and follicles, depressed serum gonadotropins and aberrant steroidogenesis, similar histopathologic features, and malignant potential.

The most unusual characteristic of the GCT in SWR mice is their occurrence in pubertal females. This is in sharp contrast to the typical spontaneous GCT in rodents which occurs in old animals. A second distinctive feature is that these tumors arise from multiple foci in ovaries that are populated by growing oocytes and follicles which is markedly different from experimental GCT induction models where oocyte depletion is accepted as the fundamental early step in tumorigenesis. GCT in older rodents is correlated with cessation of ovarian activity. Lastly, these tumors are reported to be spontaneously metastatic, which is also in contrast to reports that metastases were scarce in spontaneously occurring and in experimentally induced GCT in mice.

Histologically, GCT in SWR-derived mice can grow in either a retiform, microfollicular or macrofollicular pattern. Neoplastic cells usually have small amounts of granular amphophilic cytoplasm, small oval nuclei with coarsely clumped chromatin, single small nucleoli, and frequent mitoses. Other features may include the presence of Call- Exner-like bodies, multinucleate cells containing an iron-positive golden brown pigment, small scattered foci of osteoid (reported in 50% of the GCT) and occasional areas of luteinized thecoma. Occasionally, small rafts of neoplastic cells can be seen within lymphatic or blood vessels.

Contributor: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609- 1500.

1. Beamer WG. Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors. JNCI 77:1117-1123, 1986.

2. Beamer WG, Hoppe PC, Whitten WK. Spontaneous malignant granulosa cell tumors in ovaries of young SWR mice. Cancer Res 45:5575-5581, 1985.

3. Beamer WG, Shultz KL, Tennent BJ. Induction of ovarian granulosa cell tumors in SWRJ-9 mice with dehydroepiandrosterone. Cancer Res 48:2788-2792.

4. Tennent BJ, Beamer WG, Shultz LD, Adamson ED. Epidermal growth factor receptors in spontaneous ovarian granulosa cell tumors of SWR-derived mice. Int J Cancer 44:477-482, 1989.

5. Tennent BJ, Shultz KL, Sundberg JP, Beamer WG. Ovarian granulosa cell tumorigenesis in SWR-derived F1 hybrid mice: preneoplastic follicular abnormality and malignant disease progression. Am J Obstet Gynecol 163:626-634, 1990.

International Veterinary Pathology Slide Bank:
Laser disc frame #105-6, 120, 278-80, 289-90, 646, 1038, 1495, 1802, 8739-40.


Case II - 96-334x (AFIP 2550469), 1 photo

Signalment: Adult male Sprague Dawley rat.

History: The rat had an intraventricular cannula placed two months ago which had not been used for drug injections. The rat had been receiving regular subcutaneous injections of morphine sulfate for an experimental protocol. The rat developed dyspnea, epistaxis, diarrhea and weight loss. It was given chloramphenicol-impregnated feed.

Gross Pathology: The lung contained multiple irregularly shaped yellow-tan foci, 0.5 - 1 cm in diameter. Note: Enclosed photo is of a formalin fixed lung.

Laboratory Results: Culture of lung yielded Corynebacterium kutscheri.Acinetobacter baumannii was isolated from the lung and blood.

Contributor's Diagnosis and Comments: Pneumonia, necrosuppurative, multifocal, moderate with pleuritis and gram-positive bacilli.

Corynebacterium kutscheri is pathogenic for laboratory rats and mice. It usually occurs as a subclinical infection of the gastrointestinal tract. Disease results in abscesses in lung, preputial glands, liver and kidney from septic embolization of the bacteria. Irradiation, cortisone administration and concurrent infectious diseases can activate a subclinical infection. The bacterium is a gram-positive rod and forms irregular palisades or "Chinese letters" in tissue sections. Transmission is by the fecal-oral route.

In humans, Acinetobacter baumannii, a gram-negative coccobacillus, is an important cause of nosocomial bacteremia mainly in patients with suppressed immune responses. Diseases that occur include pneumonia, meningitis, endocarditis, peritonitis and tracheobronchitis. A. baumannii is ranked fourth as the cause of pneumonia in hospitalized patients. Acinetobacter spp. are found in soil and water and are commensals on skin and in throats of healthy people and animals. It is not a pathogen in healthy animals and in this rat it was probably a secondary infection due to the illness caused by the primary pathogen Corynebacterium kutscheri.

AFIP Diagnosis: Lung: Pneumonia, necrosuppurative, multifocal, moderate, with gram-positive bacilli, Sprague-Dawley rat, rodent.

Conference Note: The conference participants agreed with the contributor's diagnosis. A Gram stain revealed the presence of numerous gram-positive bacilli, often arranged in irregular palisades or "Chinese-letter" configuration.

Naturally occurring disease caused by Corynebacterium kutscheri appears limited to the rat (Rattus norvegicus) and mouse (Mus musculus) although the organism has been isolated from guinea pigs and hamsters. Infections occur sporadically as abscesses of superficial tissues. Lesions in epizootic rat infections develop from pulmonary embolism, whereas mouse infections more typically result in septic embolization of the joints, liver, and kidney. Although C. kutscheri can be encountered as a primary pathogen, the most common scenario is unmasking of a latent infection by experimental modulations that lower host resistance or impair immunocompetence. In addition to those listed by the contributor, ectromelia and salmonellosis, and deficiencies of vitamin B complex (particularly biotin and pantothenic acid) have been incriminated as predisposing factors.

Latent infections may not be associated with tissue lesions and C. kutscheri can often be isolated from tissues without lesions. In latently infected animals, C. kutscherimost frequently colonizes the oral cavity, cecum, colon, and rectum and rarely colonizes the lung, liver and kidney. With diminished host resistance, lesions often develop within superficial tissues, (e.g., pododermatitis, preputial gland and superficial lymph node abscesses), and middle ear. The infection can spread by hematogenous dissemination to cause microabscesses in various internal organs.

Contributor: Emory University, G70 Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322.

1. Seifert H, Strate A, Pulverer G: Nosocomial bacteremia due to Acinetobacter baumannii. Clinical features, epidemiology, and predictors of mortality. Medicine 74:340- 349, 1995.

2. Siegman-Igra Y, Bar-Yosef S, Gorea A, Avram J: Nosocomial acinetobacter meningitis secondary to invasive procedures: report of 25 cases and review. Clin Infect Dis 17:843-9, 1993.

3. Amao H, Komukai Y, Akimoto T: Natural and subclinical Corynebacterium kutscheri infection in rats. Lab Anim Sci 45:11-14, 1996.

4. Weisbroth SH: Bacterial and mycotic diseases. In The Laboratory Rat, Vol.1, Biology and Diseases. (eds) HJ Baker, JR Lindsey, SH Weisbroth, pp 214-219, 1979.

5. Amao H, Komukai Y, et al.: Natural habitats of Corynebacterium kutscheri in subclinically infected ICGN and DBA/2 strains of mice. Lab Anim Sci, 45(1):6-

International Veterinary Pathology Slide Bank:
Laser disc frame #14578.


Case III - 97/96 (AFIP 2550908), 1 photo

Signalment: Adult female Barbary ape (Macaca sylvana).

History: The Barbary ape was kept in a zoo colony. Further information was not available.

Gross Pathology: In the right hepatic lobe a well-circumscribed, grayish-brown, 9 x 7 x 4 cm nodular mass was found. Its cut surface had a sponge-like appearance, a firm, partly friable consistency and a central cystic cavity filled with mucus. The peripheral portion of the mass engulfed the right adrenal gland. A similar 3 x 2 x2 cm lesion was located in the left hepatic lobe. There were no significant lesions in other organs.

Laboratory Results: The parasitological examination of the mass revealed metacestodes of Echinococcus multilocularis.

Contributor's Diagnosis and Comments: Liver: hepatitis, severe, chronic- active, granulomatous, chronic congestion and focal necrosis, infiltrating metacestodes consistent with Echinococcus multilocularis

Echinococcus multilocularis is a member of the genus Echinococcus belonging to the family of Taeniidae. It is widely distributed in the northern hemisphere with a holarctic preponderance. The host spectrum includes different fox species, coyotes, wolves, martins, but also domestic dogs and cats. In Germany, the red fox has an infestation rate of 50-67%. Microtine rodents such as the field-mouse, voles, lemmings, and other small mammals serve as natural intermediate hosts. Man and other large animals may become intermediate hosts after intake of infectious eggs in contaminated nutrients.

The adult tapeworm is only a few millimeters long and harbored in the intestine. It consists of a scolex and a mean number of 5 segments. The prepatent period is approximately 37 days. After ingestion by the intermediate host, the onchosphere penetrates the gut wall and travels via the blood stream to the liver. Here, a metacestode (larval stage) develops as the so-called multilocular or alveolar cyst. In an adaptation to the short-lived host, E. multilocularis develops rapidly, producing protoscoleces in only 2-4 months.

Macroscopically, the growth pattern of E. multilocularis in primates simulates that of a malignant neoplasia. In the center regressive changes occur, but peripheral proliferation continues indefinitely. Thus, a progressively enlarging mass of mainly necrotic tissue with a relatively thin zone of viable proliferating parasite is produced. In the natural intermediate host, proliferation of the vesicles is curtailed with little further increase in size.

Histologically, numerous irregular small vesicles are found embedded in a dense stroma of connective tissue with focal mineralization. They are lined with a barely discernable inner germinal epithelium and prominent outer PAS-positive membrane, both of which are of parasitic origin. Intraluminal scoleces with golden-brown hooklets bud off.

In contrast, the fibrous capsule surrounding the hydatid acts as a limiting barrier in E. granulosus infection. The unbounded invasive growth of E. multilocularis is possible due to protrusions of the germinal epithelium into the surrounding hepatic tissue. Germinal cells reaching blood or lymphatic vessels can give rise to distant metastatic foci.

It remains unclear how and when this Barbary ape became infected with E. multilocularis onchospheres. To our knowledge, this is the first report of E. multilocularisinfection in a nonhuman primate. Echinococcosis in monkeys is very rare and the few reported cases involve E. granulosus.

AFIP Diagnosis: Liver: Hydatid cyst, multiloculated, with hepatocellular loss, fibrosis, and mild granulomatous hepatitis, Barbary ape (Macaca sylvana), primate. - etiology consistent with Echinococcus multilocularis.

Conference Note: The conference participants unanimously agreed with the contributor's diagnosis and comments. A literature search found that infection with Echinococcus multilocularis has been reported in a cynomolgus monkey, a gorilla, and a ring-tailed lemur.

Though Echinococcus multilocularis is principally arctic, In the United States, the cycle is found in the Northern central plains and has been reported as far south as Nebraska and Illinois.

Contributor: Institut für Veterinär-Pathologie, Frankfurter Strasse 96, D-35392 Giessen, Germany.

1. Jubb KVF; Kennedy PC; Palmer N: Pathology of Domestic Animals; Vol. 2, 4th ed, Academic Press, pp. 290-292, 1993.

2. Palotay JL, Uno: Hydatid disease in four nonhuman primates. J Am Vet Med Assoc 167:615-618, 1975.

3. Powers RD, Price RA, Houk RP, Mattlin RH: Echinococcosis in a Drill Baboon. J Am Vet Assoc 149:902-905, 1966.

4. Thompson RCA (editor): The Biology of Echinococcus and Hydatid Disease, George Allen & Unwin, pp. 6-27; 58-67, 1985.

5. Rietschel W, Kimmig P: Alveolar echinococcosis in a Cynomolgus monkey. Tierarztl Prax 22(1):85-8, 1994.

6. Urquart GM, Armour J, Duncan JL, Dunn AM and Jennings FW: Veterinary Parasitology, Longman Scientific & Technical, pp. 123-126, 1987.

7. Kondo H et. al: Alveolar hydatidosis in a gorilla and a ring-tailed lemur in Japan. J Vet Med Sci 58:447-449, 1996.

International Veterinary Pathology Slide Bank:
Laser disc frame #4185-86, 9317, 13665, 15628-9, 16409, 18907, 21405-8, 23653, 23780.


Case IV - 96-01 (AFIP 2551104

Signalment: Rabbit, Chinchilla: Chbb: CH(SPF), female, approximately 2- years- old.

History: The non-pregnant rabbit which was singly housed under standard laboratory conditions showed extensive bleeding from the vagina and died. Approximately 2 months later a second rabbit from another testing unit showed similar clinical signs and was euthanized in extremis.

Gross Pathology: Both rabbits were anemic. The heart had a slightly greyish discoloration and a mild dilation of the right ventricle. Uterus and vagina contained large amounts of partially clotted blood. Multiple cysts, approximately 0.1 to 1 cm in diameter, were observed in the uterine mucosa. Some of these cysts were small and filled with clear fluid, others were large and hemorrhagic.

Laboratory Results: No clinical or laboratory investigations were performed.

Contributor's Diagnosis and Comments:

1. Severe endometrial venous angiectasia with thrombus formation and hemorrhage - called "Endometrial venous aneurysms."
2. Mild cystic endometrial hyperplasia.

The endometrium is generally markedly compressed and has papillary projections into the lumen and bulging cysts of various diameters. These papillae and cysts are lined by a mostly single layer of low cuboidal to columnar epithelium which is ciliated at many places. Mitoses are present but not frequent. The stroma contains some inflammatory cells, predominantly granulocytes, a small amount of cellular debris and hemosiderin granules. The fluid in most endometrial cysts includes various numbers of red blood cells. In each utererine horn, a huge cyst protrudes from the mesometrial side of the horn is surrounded by a thin layer of endometrium. The internal lining of this cyst "membrane" consists of a layer of flat cells with small elongated nuclei evoking endothelial cells. Smooth muscle cells beneath the endothelium are recognizable on the side of attachment of the cyst to the uterine wall. In one of the horns the large cyst is almost completely filled with clotted blood; in the other horn it contains a thrombus in the beginning phase of organization. Some veins and lymphatic vessels in the myometrium of the more distended horn are slightly to moderately dilated.

Cystic endometrial hyperplasia is not a frequent finding in untreated rabbits except in the case of pseudopregnancy due to persistent corpora lutea. In our cases, the ovaries were unfortunately neither described grossly nor preserved for histopathologic examination so that is was not possible to establish the cause for this change.

Cases of endometrial venous aneurysms in animals were reported for the first time in 1992 by M.V. Bray et al. The authors describe the uterine lesions in 3 adult rabbits of the New Zealand white strain which presented with persistent hematuria of 1-2 days duration and were subsequently euthanized or hysterectomized. Multiple blood-filled vesicles in the mucosa were diagnosed as aneurysms of the endometrial veins. The dilated lumina contained blood or thrombi. In only one case these vascular lesions were associated with cystic endometrial hyperplasia. Urogenital bleeding in rabbits is most often related to tumors or inflammations of the genital or urinary tract. Nevertheless, endometrial aneurysms should be included in the differential diagnosis because of the dramatic consequences in the case of rupture. The etiology of endometrial aneurysms has not been established yet. Hereditary factors and congenital defects in the vessel wall are supposed to play an essential role. In our cases the two Chinchilla rabbits were obtained from the same commercial rabbitry but were not closely related.

AFIP Diagnosis: 1. Uterus, endometrium: Aneurysms, venous, multiple, with thrombosis, Chinchilla:Chbb:CH(SPF) rabbit, lagomorph.
2. Uterus: Hyperplasia, endometrial, multifocal, mild.

Conference Note: The conference participants agreed with the contibutor's diagnosis.

Contributor: Ciba-Geigy AG, Preclinical Safety, Pathology, K-135.2.26, CH-4002 Basel, Switzerland.

1. Bray MV, Weir EC, Brownstein DG, Delano ML: Endometrial venous aneurysms in three New Zealand White rabbits. Lab Anim Sci 42(4):360-362, 1992.

2. Percy DH, and Barthold SW. Hereditary Disorders-Endometrial Venous Aneurysms, In Pathology of Laboratory Rodents and Rabbits, Iowa State University Press, Ames, Iowa, pp. 221-222. 1993.

International Veterinary Pathology Slide Bank: None.

Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615

* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.

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